Prediagnostic Plasma Advanced Glycation End-products and Soluble Receptor for Advanced Glycation End-Products and Mortality in Colorectal Cancer Patients Open Access

Roshelli, Jacqueline (Spring 2021)

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Advanced glycation end-products (AGEs), formed endogenously or obtained exogenously from diet, may contribute to chronic inflammation, intracellular signaling alterations, and pathogenesis of several chronic diseases including cancer. However, the role of AGEs in cancer survival is less known.

In this study, the associations of pre-diagnostic circulating AGEs and soluble receptor for AGEs (sRAGE) with colorectal cancer (CRC)-specific and overall mortality were estimated using multivariable Cox proportional hazards regression among 1,369 CRC cases in the European Prospective Investigation into Cancer and Nutrition study. Plasma concentrations of AGEs and sRAGE were measured on average 53 months before CRC diagnosis using ultra performance liquid chromatography tandem mass spectrometry.

Over a mean follow‐up period of 53 months, 693 deaths occurred of which 541 (78%) were due to CRC. Plasma AGEs, individually or combined, were not statistically significantly associated with CRC-specific or overall mortality. However, a possible interaction by sex was suggested for carboxyethyl lysine (CEL) and CRC-specific mortality, with a positive association observed among women only (Pinteraction=0.05). CRC cases with higher sRAGE concentrations were at higher risk of dying from CRC (hazard ratio, HRQ5 vs Q1=1.67, 95% CI:1.21-2.30, Ptrend≤0.01) or any cause (HRQ5 vs Q1=1.38, 95% CI:1.05-1.83, Ptrend≤0.01). These associations tended to be stronger among cases with type II diabetes.

In conclusion, pre-diagnostic circulating concentrations of AGEs were not associated with CRC-specific and overall mortality in CRC patients. However, a positive association was observed between sRAGE and CRC-specific and overall mortality. Further studies in other settings and exploring potential effect modification by sex and diabetes are needed. Our findings may stimulate further research on AGEs’ role in survival among cancer patients.  

Table of Contents

Chapter I. Background________________________________________________________________1

Chapter II. Manuscript _______________________________________________________________ 9

Chapter III. Public Health Implications and Possible Future Directions________________________ 25

References________________________________________________________________________ 26

Figures and tables __________________________________________________________________31

Supplementary figures and tables _____________________________________________________42

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